Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019045 (hemoglobinopathies)
 2,704 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This report concerns the detection of two abnormal hemoglobins (Hb), Hb Manitoba and Hb G Coushatta, during analysis for glycohemoglobin (Hb A1c). Blood samples from two diabetic patients, analyzed for Hb A1c by HPLC, were found to contain additional Hb peaks. The presence of an abnormal Hb was confirmed in both instances by hemoglobinopathy studies. Structural studies determined the two Hb variants to be Hb Manitoba (alpha 2 102 Ser----Arg beta 2) and Hb G-Coushatta (alpha 2 beta 2 22 Glu----Ala). The significance of the presence of an abnormal Hb in Hb A1c analysis is discussed.
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PMID:Detection of two abnormal hemoglobins, Hb Manitoba and Hb G-Coushatta, during analysis of glycohemoglobin (A1c) by high-performance liquid chromatography. 137 26

We have developed a murine monoclonal antibody (mAb) specific for the delta chain of hemoglobin (Hb) A2 that does not cross-react with alpha, beta, or gamma chains. The mAb reacted with Hb P-Nilotic (beta delta hybrid), but not with Hb Lepore-Boston (delta beta hybrid), indicating an epitope consisting of positions 116 (Arg) and 117 (Asn) or 125 (Gln) and 126 (Met) of the delta chain. By using this antibody, we have established a simple and rapid enzyme-linked immunosorbent assay (ELISA) for the detection and quantification of Hb A2 in adult, cord, and fetal hemolysates. We analyzed 70 adult, 8 newborn, and 19 fetal hemolysates from normal subjects and those with various hemoglobinopathies. The mean percentage of Hb A2 was 2.5 for normal adults, 5.4 for beta thalassemic (beta thal) heterozygotes, and less than 0.1% in beta thal fetal samples. We were able to distinguish and characterize certain phenotypes of beta thal patients such as beta thal heterozygotes, beta 0 thal homozygotes, and C beta 0 thal, and C beta + thal double heterozygotes with the aid of this and other mAbs we have generated. This technique is a valuable addition to current methods for the diagnosis of beta thal based on quantification of Hb A2.
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PMID:Application of a monoclonal antibody specific for the delta chain of hemoglobin A2 in the diagnosis of beta thalassemia. 195 20

Sogn hemoglobinopathy was identified in a young American woman and in a young American man of apparently unrelated families of Norwegian ancestry. Both persons were asymptomatic and without clinical or hematologic manifestations. Hemoglobin Sogn, beta(A11)14 Leu----Arg, is an unstable hemoglobin that may easily be mistaken for hemoglobin S, G, or D by alkaline hemoglobin electrophoresis. These are the first known instances of hemoglobin Sogn outside of Norway. Oxygen affinity is normal. Sogn hemoglobinopathy is an incidental finding that has no adverse implication for the health of heterozygotes.
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PMID:Two families with hemoglobin Sogn, beta(A11)14 Leu----Arg, in Minnesota and Indiana: hematologic, functional, and biosynthetic features. 219 50

Hemoglobin Pasadena [beta 75(E19)Leu----Arg] was found in a boy who had an acute episode of anemia and rapid splenic enlargement. His father was the only other member of a large family with this hemoglobinopathy. We have used gene mapping techniques for direct identification of the beta-globin gene mutation. To correlate the DNA findings with the structural identification of this variant, we have also performed globin chain separation and analysis of the tryptic peptides using high performance liquid chromatography and secondary ion mass spectral analysis.
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PMID:Hemoglobin Pasadena: identification of the gene mutant by DNA analysis using synthetic DNA probes. 334 4

The inherited beta-hemoglobinopathies (sickle cell disease and beta thalassemia) are the result of a mutation in the adult (beta) globin gene. The fetal globin chain, encoded by the gamma globin genes, can substitute for the mutated or defective beta globin chain, but expression of the gamma globin gene is developmentally inactivated prior to birth. Re-inducing expression of the normal fetal globin genes is a preferred method of ameliorating sickle cell disease and the beta thalassemias. Stimulation of as little as 4-8% fetal globin synthesis in the bone marrow can produce > 20% fetal hemoglobin in the peripheral circulation, due to enhanced survival of red blood cells containing both sickle and fetal hemoglobin, compared to those containing sickle hemoglobin alone. Butyric acid and butyrate derivatives are generally safe compounds which induce fetal hemoglobin production by stimulating the promoter of the fetal globin genes. An initial trial with the parent compound, delivered as Arginine Butyrate, has demonstrated rapid stimulation of fetal globin expression to levels that have been shown to ameliorate these conditions. Phase 1 trials of an oral butyrate derivative with a long plasma half-life have just begun. These agents now provide a specific new approach for ameliorating these classic molecular disorders and merit further investigation in larger patient populations.
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PMID:Butyrate-induced reactivation of the fetal globin genes: a molecular treatment for the beta-hemoglobinopathies. 768 3

Hb Val de Marne [alpha 133(H16)Ser-->Arg] was found in a French family during a neonatal hemoglobinopathy screening program. The abnormal hemoglobin was found, within a few months interval, in two newborn children who were first cousins. In the children as well as in the parents carrying this hemoglobin variant, the red cell parameters were normal. Hb Val de Marne, isolated by isoelectrofocusing, displayed a slightly higher auto-oxidation rate than Hb A. Its oxygen affinity was increased 1.7-fold in comparison to that of Hb A. The heterotropic effects were normal.
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PMID:Hb Val de Marne [alpha 133(H16)Ser-->Arg]: a new hemoglobin variant with moderate increase in oxygen affinity. 829

Microscale analysis of a variant hemoglobin (Hb) has been achieved by combination of high performance liquid chromatography (HPLC) and electrospray mass spectrometry (ESMS) and the method should be almost universally applicable. We have eliminated preparative scale HPLC of globin chains and semi-preparative HPLC of proteolytic digests which had been used prior to mass spectrometry. Use of microbore HPLC columns reduced the time required for analysis substantially and solvent usage by 100x. Molecular masses of intact globins and masses and sequence information of tryptic peptides could be obtained without collecting and separately analyzing chromatographic fractions. As an example of the use of these methods, we report the characterization of an unknown hemoglobinopathy case that was finally authenticated as Hb P-Galveston [beta 117(G19)His-->Arg], using the following sequence of analyses: 1) ESMS of complete hemolysate, 2) analytical HPLC of globin chains, 3) combined microbore HPLC/ESMS of globin chains to determine their molecular masses, 4) cysteine derivatization and tryptic digestion of mixture of all globins, followed by microbore separation of the peptides, molecular mass determination, and generation of fragmentation patterns allowing confirmation of amino acid sequences. This four-part strategy should allow characterization of almost all variant Hbs. Exceptions would be mutations in regions of globin chains which give rise to small (< four residues) tryptic peptides, either normal or produced by addition of new tryptic sites and mutations that introduce only minute difference in molecular weight (MW) of tryptic peptides. Since only 10% of each separated peptides is mass analyzed, 90% is available for collection and further structural identification (e.g. by tandem MS or Edman sequencing) if the identity is still in doubt.
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PMID:Expediting rare variant hemoglobin characterization by combined HPLC/electrospray mass spectrometry. 833 Sep 75

A young woman aged 21 was found to be a new carrier of Hb-Belfast: beta 15 (A 12) Trp-->Arg, and the characteristics of her hemoglobinopathy were not different from those of the four cases so far described: mild hemolysis with molecular instability of the abnormal Hb, red cells inclusion bodies, and slight alterations of some functional parameters of whole blood. On this occasion, direct DNA analysis indicated the genomic nucleotide replacement of the disease: TGG-AGG. This was inherited by the mother, originating from Bari (Apulia).
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PMID:Direct DNA analysis in a new Italian carrier of Hb-Belfast: beta 15 (A12) Trp-->Arg. 1144 85

Hemoglobin (Hb) chains have been analyzed traditionally by cellulose acetate electrophoresis after sample extraction with acetone and denaturation with concentrated urea in order to detect thalassemia (Thal). A few capillary electrophoresis (CE) methods have been also described for separation of Hb chains also after sample extraction. We describe a CE method for analysis of Hb chains without sample preparation. Red blood cells were diluted (hemolyzed) in water and injected directly onto the capillary. The separation was performed in concentrated phosphate buffer at pH 12.6 and 2.15. Under these conditions of pH and buffer concentration, the chains were denatured and separated from the heme during electrophoresis. The common variants of the beta-chains, such as beta(S), beta(C), and beta(E), are also separated from each other. The intact Hb molecule is analyzed using the same sample and CE conditions but in an arginine-Tris buffer, pH 8.6. The data from the three separations are used to complement each other for interpretation of the presence of Hb variants and for thalassemia. The main advantages of this method are simplicity and speed. This method illustrates the flexibility and simplicity of the CE for analysis of the hemoglobinopathies.
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PMID:Simplified hemoglobin chain detection by capillary electrophoresis. 1569 Apr 30

We report an unusual north Indian patient with Hemoglobin Evanston [alpha 14 (A12) Try --> Arg] who had acquired cyclic thrombocytopenia (10-1230 x 10(9)/l periodic oscillation of four week duration) which recovered without any specific therapy. She later developed Takayasu's disease and underwent three corrective stents. She is presently in clinical remission and is on regular follow up. To the best of our knowledge our patient is the first report of Hb Evanston from the indigenous population of India and highlights the need to look for point mutations in the alpha globin gene, which may interact with thalassemia or other hemoglobinopathies, in atypical cases. The association of these three disorders in our patient is possibly unrelated though an immune basis for the cyclic thrombocytopenia and Takayasu's disease is likely as seen in this report.
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PMID:Investigation of persistent hypochromic microcytosis unmasks hemoglobin Evanston [alpha 14 (A12) Try--> Arg] in a patient of cyclic thrombocytopenia preceding Takayasu's disease. 1627 37


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